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斑马鱼作为生物测定导向的神经疾病天然产物药物发现的新兴模型。

Zebrafish as an Emerging Model for Bioassay-Guided Natural Product Drug Discovery for Neurological Disorders.

作者信息

Pitchai Arjun, Rajaretinam Rajesh Kannan, Freeman Jennifer L

机构信息

Molecular and Nanomedicine Research Unit (MNRU), Centre for Nanoscience and Nanotechnology (CNSNT), Sathyabama Institute of Science and Technology, Chennai 600119, Tamil Nadu, India.

School of Health Sciences, Purdue University, West Lafayette, IN 47907, USA.

出版信息

Medicines (Basel). 2019 May 30;6(2):61. doi: 10.3390/medicines6020061.

Abstract

Most neurodegenerative diseases are currently incurable, with large social and economic impacts. Recently, there has been renewed interest in investigating natural products in the modern drug discovery paradigm as novel, bioactive small molecules. Moreover, the discovery of potential therapies for neurological disorders is challenging and involves developing optimized animal models for drug screening. In contemporary biomedicine, the growing need to develop experimental models to obtain a detailed understanding of malady conditions and to portray pioneering treatments has resulted in the application of zebrafish to close the gap between in vitro and in vivo assays. Zebrafish in pharmacogenetics and neuropharmacology are rapidly becoming a widely used organism. Brain function, dysfunction, genetic, and pharmacological modulation considerations are enhanced by both larval and adult zebrafish. Bioassay-guided identification of natural products using zebrafish presents as an attractive strategy for generating new lead compounds. Here, we see evidence that the zebrafish's central nervous system is suitable for modeling human neurological disease and we review and evaluate natural product research using zebrafish as a vertebrate model platform to systematically identify bioactive natural products. Finally, we review recently developed zebrafish models of neurological disorders that have the potential to be applied in this field of research.

摘要

大多数神经退行性疾病目前无法治愈,会产生巨大的社会和经济影响。最近,在现代药物发现模式中,人们对研究天然产物作为新型生物活性小分子重新产生了兴趣。此外,发现神经疾病的潜在疗法具有挑战性,涉及开发用于药物筛选的优化动物模型。在当代生物医学中,越来越需要开发实验模型以详细了解疾病状况并描绘开创性治疗方法,这导致斑马鱼被用于弥合体外和体内试验之间的差距。斑马鱼在药物遗传学和神经药理学中正迅速成为一种广泛使用的生物体。幼体和成体斑马鱼都有助于对脑功能、功能障碍、遗传和药理调节进行研究。使用斑马鱼进行生物测定指导的天然产物鉴定是生成新先导化合物的一种有吸引力的策略。在此,我们看到证据表明斑马鱼的中枢神经系统适合模拟人类神经疾病,并且我们回顾和评估了使用斑马鱼作为脊椎动物模型平台来系统鉴定生物活性天然产物的天然产物研究。最后,我们回顾了最近开发的有可能应用于该研究领域的神经疾病斑马鱼模型。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a5f3/6631710/5c15cbb9e2c3/medicines-06-00061-g001.jpg

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